UA75891C2 - Pharmaceutically active sulfonamides derivatives having either lipophilic fragments and those capable to ionize as inhibitors of protein- jun-kinases, a pharmaceutical composition, a method for obtaining these compounds (variants) and intermediary compounds - Google Patents
Pharmaceutically active sulfonamides derivatives having either lipophilic fragments and those capable to ionize as inhibitors of protein- jun-kinases, a pharmaceutical composition, a method for obtaining these compounds (variants) and intermediary compounds Download PDFInfo
- Publication number
- UA75891C2 UA75891C2 UA2003032606A UA2003032606A UA75891C2 UA 75891 C2 UA75891 C2 UA 75891C2 UA 2003032606 A UA2003032606 A UA 2003032606A UA 2003032606 A UA2003032606 A UA 2003032606A UA 75891 C2 UA75891 C2 UA 75891C2
- Authority
- UA
- Ukraine
- Prior art keywords
- amino
- thien
- sulfonyl
- methyl
- benzamide
- Prior art date
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00810887A EP1193268A1 (en) | 2000-09-27 | 2000-09-27 | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases |
| PCT/IB2001/001772 WO2002026733A2 (en) | 2000-09-27 | 2001-09-27 | sHARMACEUTICALLY ACTIVE SULFONAMIDE DERIVATIVES BEARING BOTH LIPOPHILIC AND IONISABLE MOIETIES AS INHIBITORS OF PROTEIN JUNKINASES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA75891C2 true UA75891C2 (en) | 2006-06-15 |
Family
ID=8174937
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2003032606A UA75891C2 (en) | 2000-09-27 | 2001-09-27 | Pharmaceutically active sulfonamides derivatives having either lipophilic fragments and those capable to ionize as inhibitors of protein- jun-kinases, a pharmaceutical composition, a method for obtaining these compounds (variants) and intermediary compounds |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US7544700B2 (no) |
| EP (2) | EP1193268A1 (no) |
| JP (1) | JP4927304B2 (no) |
| KR (1) | KR20030057532A (no) |
| CN (1) | CN1288150C (no) |
| AR (1) | AR033999A1 (no) |
| AU (2) | AU8799101A (no) |
| BG (1) | BG107633A (no) |
| BR (1) | BR0114223A (no) |
| CA (1) | CA2421209A1 (no) |
| CZ (1) | CZ2003884A3 (no) |
| EA (1) | EA005819B1 (no) |
| EE (1) | EE200300119A (no) |
| ES (1) | ES2438185T3 (no) |
| HK (1) | HK1072768A1 (no) |
| HR (1) | HRP20030214A2 (no) |
| HU (1) | HUP0302980A3 (no) |
| IL (1) | IL154965A0 (no) |
| MX (1) | MXPA03002568A (no) |
| NO (1) | NO20031375D0 (no) |
| NZ (1) | NZ524542A (no) |
| PL (1) | PL361687A1 (no) |
| SK (1) | SK3662003A3 (no) |
| UA (1) | UA75891C2 (no) |
| WO (1) | WO2002026733A2 (no) |
| YU (1) | YU21803A (no) |
| ZA (1) | ZA200301746B (no) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1193256A1 (en) * | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active benzsulfonamide derivatives as inhibitors of JNK proteins |
| EP1193267A1 (en) * | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active hydrophilic sulfonamide derivatives as inhibitors of protein JunKinases |
| EP1193268A1 (en) | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases |
| ATE419247T1 (de) * | 2001-07-23 | 2009-01-15 | Serono Lab | Arylsulfonamidderivate als hemmer c-jun- terminaler kinasen (jnk) |
| EP1663193B1 (en) | 2003-09-12 | 2012-04-04 | Merck Serono SA | Sulfonamide derivatives for the treatment of diabetes |
| MXPA06007172A (es) * | 2003-12-23 | 2006-08-23 | Lundbeck & Co As H | Derivados de 2-(1h-indolilsulfanil)-bencilamina como ssri. |
| AR052308A1 (es) * | 2004-07-16 | 2007-03-14 | Lundbeck & Co As H | Derivados de 2-(1h-indolilsulfanil)-arilamina y una composicion farmaceutica que contiene al compuesto |
| US7629473B2 (en) * | 2005-06-17 | 2009-12-08 | H. Lundbeck A/S | 2-(1H-indolylsulfanyl)-aryl amine derivatives |
| AR054393A1 (es) * | 2005-06-17 | 2007-06-20 | Lundbeck & Co As H | Derivados de benzo(b)furano y benzo(b)tiofeno, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por la inhibicion de la reabsorcion de neurotransmisores de amina biogenicos. |
| BRPI0613042A2 (pt) | 2005-07-15 | 2010-12-14 | Serono Lab | inibidores de jnk para o tratamento de endometriose |
| KR20080044836A (ko) | 2005-07-15 | 2008-05-21 | 라보라뚜와르 세로노 에스. 에이. | 자궁내막증 치료용 ｊｎｋ 억제제 |
| AU2011265521B9 (en) * | 2005-07-15 | 2014-05-22 | Merck Serono Sa | JNK inhibitors for the treatment of endometreosis |
| EP2026802A2 (en) * | 2006-06-02 | 2009-02-25 | Laboratoires Serono SA | Jnk inhibitors for treatment of skin diseases |
| WO2010043721A1 (en) | 2008-10-17 | 2010-04-22 | Oryzon Genomics, S.A. | Oxidase inhibitors and their use |
| EP2389362B1 (en) | 2009-01-21 | 2019-12-11 | Oryzon Genomics, S.A. | Phenylcyclopropylamine derivatives and their medical use |
| KR101736218B1 (ko) | 2009-09-25 | 2017-05-16 | 오리존 지노믹스 에스.에이. | 라이신 특이적 디메틸라아제-1 억제제 및 이의 용도 |
| EP2486002B1 (en) | 2009-10-09 | 2019-03-27 | Oryzon Genomics, S.A. | Substituted heteroaryl- and aryl- cyclopropylamine acetamides and their use |
| WO2011106105A2 (en) | 2010-02-24 | 2011-09-01 | Oryzon Genomics, S.A. | Inhibitors for antiviral use |
| WO2011106573A2 (en) | 2010-02-24 | 2011-09-01 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for diseases and disorders associated with hepadnaviridae |
| ES2607081T3 (es) | 2010-04-19 | 2017-03-29 | Oryzon Genomics, S.A. | Inhibidores de desmetilasa específica de lisina-1 y su uso |
| HUE037937T2 (hu) | 2010-07-29 | 2021-11-29 | Oryzon Genomics Sa | Arilciklopropilamin-alapú LSD1-demetiláz inhibitorok és gyógyászati alkalmazásuk |
| US9006449B2 (en) | 2010-07-29 | 2015-04-14 | Oryzon Genomics, S.A. | Cyclopropylamine derivatives useful as LSD1 inhibitors |
| US9061966B2 (en) | 2010-10-08 | 2015-06-23 | Oryzon Genomics S.A. | Cyclopropylamine inhibitors of oxidases |
| WO2012072713A2 (en) | 2010-11-30 | 2012-06-07 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for diseases and disorders associated with flaviviridae |
| WO2012107498A1 (en) | 2011-02-08 | 2012-08-16 | Oryzon Genomics S.A. | Lysine demethylase inhibitors for myeloproliferative disorders |
| US20140296255A1 (en) * | 2011-05-19 | 2014-10-02 | Oryzong Genomics, S.A. | Lysine demethylase inhibitors for thrombosis and cardiovascular diseases |
| EP2741741A2 (en) * | 2011-05-19 | 2014-06-18 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for inflammatory diseases or conditions |
| EP2768805B1 (en) | 2011-10-20 | 2020-03-25 | Oryzon Genomics, S.A. | (hetero)aryl cyclopropylamine compounds as lsd1 inhibitors |
| PE20141692A1 (es) | 2011-10-20 | 2014-11-08 | Oryzon Genomics Sa | Compuestos de (hetero) aril ciclopropilamina como inhibidores de lsd1 |
| KR101699822B1 (ko) | 2011-12-21 | 2017-01-25 | 노비라 테라퓨틱스, 인코포레이티드 | B형 간염의 항바이러스성 제제 |
| AR092270A1 (es) | 2012-08-28 | 2015-04-08 | Janssen R&D Ireland | Sulfamoilarilamidas y su uso como medicamentos para el tratamiento de la hepatitis b |
| PT2961732T (pt) | 2013-02-28 | 2017-06-26 | Janssen Sciences Ireland Uc | Sulfamoil-arilamidas e utilização das mesmas como medicamentos para o tratamento de hepatite b |
| EA027068B1 (ru) | 2013-04-03 | 2017-06-30 | Янссен Сайенсиз Айрлэнд Юси | Производные n-фенилкарбоксамида и их применение в качестве лекарственных препаратов для лечения гепатита b |
| JP6441315B2 (ja) | 2013-05-17 | 2018-12-19 | ヤンセン・サイエンシズ・アイルランド・ユーシー | スルファモイルチオフェンアミド誘導体およびｂ型肝炎を治療するための医薬品としてのその使用 |
| JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
| US10450270B2 (en) | 2013-07-25 | 2019-10-22 | Janssen Sciences Ireland Uc | Glyoxamide substituted pyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| MX368158B (es) | 2013-10-23 | 2019-09-20 | Janssen Sciences Ireland Uc | Derivados de carboxamida y su uso como medicamentos para el tratamiento de la hepatitis b. |
| US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| MX2016009449A (es) | 2014-02-05 | 2016-10-13 | Novira Therapeutics Inc | Terapia de combinacion para el tratamiento de infecciones por virus de la hepatitis b (vhb). |
| EA035848B1 (ru) | 2014-02-06 | 2020-08-20 | Янссен Сайенсиз Айрлэнд Юси | Производные сульфамоилпирроламида и их применение в качестве медикаментов для лечения гепатита b |
| WO2016149581A1 (en) | 2015-03-19 | 2016-09-22 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis b infections |
| US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| AU2016330964B2 (en) | 2015-09-29 | 2021-04-01 | Novira Therapeutics, Inc. | Crystalline forms of a hepatitis B antiviral agent |
| SG11201808949SA (en) | 2016-04-15 | 2018-11-29 | Novira Therapeutics Inc | Combinations and methods comprising a capsid assembly inhibitor |
| CA3090125A1 (en) | 2018-03-14 | 2019-09-19 | Janssen Sciences Ireland Unlimited Company | Capsid assembly modulator dosing regimen |
| US11096931B2 (en) | 2019-02-22 | 2021-08-24 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of HBV infection or HBV-induced diseases |
| EP3966205A1 (en) | 2019-05-06 | 2022-03-16 | Janssen Sciences Ireland Unlimited Company | Amide derivatives useful in the treatment of hbv infection or hbv-induced diseases |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2553414B1 (fr) * | 1983-10-18 | 1986-08-14 | Choay Sa | Nouveaux benzenesulfonamides n-cyclises, leur procede de preparation et leur utilisation comme substance active de compositions pharmaceutiques |
| US5238950A (en) * | 1991-12-17 | 1993-08-24 | Schering Corporation | Inhibitors of platelet-derived growth factor |
| US5744320A (en) | 1995-06-07 | 1998-04-28 | Promega Corporation | Quenching reagents and assays for enzyme-mediated luminescence |
| CN1159292C (zh) * | 1996-05-31 | 2004-07-28 | 法玛西雅厄普约翰美国公司 | 用作选择性多巴胺d3配体的芳基取代的环胺类化合物 |
| US6043083A (en) | 1997-04-28 | 2000-03-28 | Davis; Roger J. | Inhibitors of the JNK signal transduction pathway and methods of use |
| CA2291778A1 (en) * | 1997-05-29 | 1998-12-03 | Merck & Co., Inc. | Heterocyclic amide compounds as cell adhesion inhibitors |
| DE19743435A1 (de) * | 1997-10-01 | 1999-04-08 | Merck Patent Gmbh | Benzamidinderivate |
| AR019322A1 (es) * | 1998-06-18 | 2002-02-13 | Smithkline Beecham Corp | Derivados de sulfonilo sustituido por heterociclo-etanodionanilina sustituida por heterociclo, composicion farmaceutica que los contiene y su uso para lamanufactura de un medicamento |
| CN1332943C (zh) * | 1998-07-08 | 2007-08-22 | 萨诺费－阿文蒂斯德国有限公司 | 硫取代的磺酰基氨基羧酸n－芳基酰胺,其制备方法、用途以及含有该化合物的药物制剂 |
| EP1088821A1 (en) * | 1999-09-28 | 2001-04-04 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonamide derivatives |
| EP1193268A1 (en) | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases |
| EP1193267A1 (en) * | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active hydrophilic sulfonamide derivatives as inhibitors of protein JunKinases |
| EP1193256A1 (en) * | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active benzsulfonamide derivatives as inhibitors of JNK proteins |
-
2000
- 2000-09-27 EP EP00810887A patent/EP1193268A1/en not_active Withdrawn
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2001
- 2001-09-27 ZA ZA200301746A patent/ZA200301746B/en unknown
- 2001-09-27 EE EEP200300119A patent/EE200300119A/xx unknown
- 2001-09-27 IL IL15496501A patent/IL154965A0/xx unknown
- 2001-09-27 SK SK366-2003A patent/SK3662003A3/sk not_active Application Discontinuation
- 2001-09-27 PL PL36168701A patent/PL361687A1/xx not_active Application Discontinuation
- 2001-09-27 BR BR0114223-2A patent/BR0114223A/pt not_active IP Right Cessation
- 2001-09-27 AR ARP010104565A patent/AR033999A1/es unknown
- 2001-09-27 AU AU8799101A patent/AU8799101A/xx active Pending
- 2001-09-27 JP JP2002531117A patent/JP4927304B2/ja not_active Expired - Fee Related
- 2001-09-27 KR KR10-2003-7004265A patent/KR20030057532A/ko not_active Application Discontinuation
- 2001-09-27 AU AU2001287991A patent/AU2001287991B2/en not_active Ceased
- 2001-09-27 EP EP01967622.0A patent/EP1322642B1/en not_active Expired - Lifetime
- 2001-09-27 CZ CZ2003884A patent/CZ2003884A3/cs unknown
- 2001-09-27 US US10/381,665 patent/US7544700B2/en not_active Expired - Fee Related
- 2001-09-27 CA CA002421209A patent/CA2421209A1/en not_active Abandoned
- 2001-09-27 CN CNB01819141XA patent/CN1288150C/zh not_active Expired - Fee Related
- 2001-09-27 ES ES01967622.0T patent/ES2438185T3/es not_active Expired - Lifetime
- 2001-09-27 EA EA200300412A patent/EA005819B1/ru not_active IP Right Cessation
- 2001-09-27 UA UA2003032606A patent/UA75891C2/uk unknown
- 2001-09-27 YU YU21803A patent/YU21803A/sh unknown
- 2001-09-27 NZ NZ524542A patent/NZ524542A/en unknown
- 2001-09-27 MX MXPA03002568A patent/MXPA03002568A/es not_active Application Discontinuation
- 2001-09-27 HU HU0302980A patent/HUP0302980A3/hu unknown
- 2001-09-27 WO PCT/IB2001/001772 patent/WO2002026733A2/en active IP Right Grant
-
2003
- 2003-03-13 BG BG107633A patent/BG107633A/bg unknown
- 2003-03-20 HR HR20030214A patent/HRP20030214A2/hr not_active Application Discontinuation
- 2003-03-26 NO NO20031375A patent/NO20031375D0/no not_active Application Discontinuation
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2005
- 2005-04-29 HK HK05103676A patent/HK1072768A1/xx not_active IP Right Cessation
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